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1.
Shiffman D Trompet S Louie JZ Rowland CM Catanese JJ Iakoubova OA Kirchgessner TG Westendorp RG de Craen AJ Slagboom PE Buckley BM Stott DJ Sattar N Devlin JJ Packard CJ Ford I Sacks FM Jukema JW 《PloS one》2012,7(5):e38240
Statin therapy reduces the risk of coronary heart disease (CHD), however, the person-to-person variability in response to statin therapy is not well understood. We have investigated the effect of genetic variation on the reduction of CHD events by pravastatin. First, we conducted a genome-wide association study of 682 CHD cases from the Cholesterol and Recurrent Events (CARE) trial and 383 CHD cases from the West of Scotland Coronary Prevention Study (WOSCOPS), two randomized, placebo-controlled studies of pravastatin. In a combined case-only analysis, 79 single nucleotide polymorphisms (SNPs) were associated with differential CHD event reduction by pravastatin according to genotype (P<0.0001), and these SNPs were analyzed in a second stage that included cases as well as non-cases from CARE and WOSCOPS and patients from the PROspective Study of Pravastatin in the Elderly at Risk/PHArmacogenomic study of Statins in the Elderly at risk for cardiovascular disease (PROSPER/PHASE), a randomized placebo controlled study of pravastatin in the elderly. We found that one of these SNPs (rs13279522) was associated with differential CHD event reduction by pravastatin therapy in all 3 studies: P = 0.002 in CARE, P = 0.01 in WOSCOPS, P = 0.002 in PROSPER/PHASE. In a combined analysis of CARE, WOSCOPS, and PROSPER/PHASE, the hazard ratio for CHD when comparing pravastatin with placebo decreased by a factor of 0.63 (95% CI: 0.52 to 0.75) for each extra copy of the minor allele (P = 4.8 × 10(-7)). This SNP is located in DnaJ homolog subfamily C member 5B (DNAJC5B) and merits investigation in additional randomized studies of pravastatin and other statins. 相似文献
2.
Brautbar A Virani SS Belmont J Nambi V Jones PH Ballantyne CM 《Journal of lipid research》2012,53(3):556-560
ApoC-III is a proatherogenic protein associated with elevated triglycerides; its deficiency is associated with reduced atherosclerosis. Mixed dyslipidemia, characterized by elevated triglyceride and apoC-III levels and low HDL cholesterol level, with or without elevated LDL cholesterol, increases cardiovascular disease risk and is commonly treated with combined statin and fibrate therapy. We sought to identify single nucleotide polymorphisms (SNPs) associated with apoC-III level response to combination therapy with statins and fenofibric acid (FA) in individuals with mixed dyslipidemia. Participants (n = 1,250) in a multicenter, randomized, double-blind, active-controlled study examining response to FA alone and in combination with statin were genotyped for candidate SNPs. Multivariate linear regression and two-way ANOVA for percent change in apoC-III level were performed. SNPs in the lipoprotein lipase (LPL) gene region, rs1801177 (P = 4.7 × 10(-8)), rs7016529 (P = 1.2 × 10(-6)), and rs249 (P = 4.1 × 10(-5)), were associated with apoC-III response to combination therapy. A haplotype composed of the minor alleles of these SNPs, with 2% population frequency, was associated with an unexpected apoC-III increase in response to statins and FA. This is the first report to show that genetic variation within the LPL gene region can affect the response of apoC-III levels to combined statin and FA therapy. 相似文献
3.
Cécilia G. Maubaret Klelia D. Salpea Casey E. Romanoski Lasse Folkersen Jackie A. Cooper Coralea Stephanou Ka Wah Li Jutta Palmen Anders Hamsten Andrew Neil Jeffrey W. Stephens Aldons J. Lusis Per Eriksson Philippa J. Talmud Steve E. Humphries the Simon Broome Research Group the EARSII consortium 《PloS one》2013,8(12)
Objective
To replicate the associations of leukocyte telomere length (LTL) with variants at four loci and to investigate their associations with coronary heart disease (CHD) and type II diabetes (T2D), in order to examine possible causal effects of telomere maintenance machinery on disease aetiology.Methods
Four SNPs at three loci BICD1 (rs2630578 GγC), 18q12.2 (rs2162440 GγT), and OBFC1 (rs10786775 CγG, rs11591710 AγC) were genotyped in four studies comprised of 2353 subjects out of which 1148 had CHD and 566 T2D. Three SNPs (rs12696304 CγG, rs10936601G>T and rs16847897 GγC) at the TERC locus were genotyped in these four studies, in addition to an offspring study of 765 healthy students. For all samples, LTL had been measured using a real-time PCR-based method.Results
Only one SNP was associated with a significant effect on LTL, with the minor allele G of OBFC1 rs10786775 SNP being associated with longer LTL (β=0.029, P=0.04). No SNPs were significantly associated with CHD or T2D. For OBFC1 the haplotype carrying both rare alleles (rs10786775G and rs11591710C, haplotype frequency 0.089) was associated with lower CHD prevalence (OR: 0.77; 95% CI: 0.61–0.97; P= 0.03). The TERC haplotype GTC (rs12696304G, rs10936601T and rs16847897C, haplotype frequency 0.210) was associated with lower risk for both CHD (OR: 0.86; 95% CI: 0.75-0.99; P=0.04) and T2D (OR: 0.74; 95% CI: 0.61–0.91; P= 0.004), with no effect on LTL. Only the last association remained after adjusting for multiple testing.Conclusion
Of reported associations, only that between the OBFC1 rs10786775 SNP and LTL was confirmed, although our study has a limited power to detect modest effects. A 2-SNP OBFC1 haplotype was associated with higher risk of CHD, and a 3-SNP TERC haplotype was associated with both higher risk of CHD and T2D. Further work is required to confirm these results and explore the mechanisms of these effects. 相似文献4.
Deshmukh HA Colhoun HM Johnson T McKeigue PM Betteridge DJ Durrington PN Fuller JH Livingstone S Charlton-Menys V Neil A Poulter N Sever P Shields DC Stanton AV Chatterjee A Hyde C Calle RA Demicco DA Trompet S Postmus I Ford I Jukema JW Caulfield M Hitman GA;CARDS ASCOT PROSPER Investigators 《Journal of lipid research》2012,53(5):1000-1011
We carried out a genome-wide association study (GWAS) of LDL-c response to statin using data from participants in the Collaborative Atorvastatin Diabetes Study (CARDS; n = 1,156), the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT; n = 895), and the observational phase of ASCOT (n = 651), all of whom were prescribed atorvastatin 10 mg. Following genome-wide imputation, we combined data from the three studies in a meta-analysis. We found associations of LDL-c response to atorvastatin that reached genome-wide significance at rs10455872 (P = 6.13 × 10(-9)) within the LPA gene and at two single nucleotide polymorphisms (SNP) within the APOE region (rs445925; P = 2.22 × 10(-16) and rs4420638; P = 1.01 × 10(-11)) that are proxies for the ε2 and ε4 variants, respectively, in APOE. The novel association with the LPA SNP was replicated in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial (P = 0.009). Using CARDS data, we further showed that atorvastatin therapy did not alter lipoprotein(a) [Lp(a)] and that Lp(a) levels accounted for all of the associations of SNPs in the LPA gene and the apparent LDL-c response levels. However, statin therapy had a similar effect in reducing cardiovascular disease (CVD) in patients in the top quartile for serum Lp(a) levels (HR = 0.60) compared with those in the lower three quartiles (HR = 0.66; P = 0.8 for interaction). The data emphasize that high Lp(a) levels affect the measurement of LDL-c and the clinical estimation of LDL-c response. Therefore, an apparently lower LDL-c response to statin therapy may indicate a need for measurement of Lp(a). However, statin therapy seems beneficial even in those with high Lp(a). 相似文献
5.
《Journal of cellular and molecular medicine》2021,25(16):8047
Irritable bowel syndrome (IBS) is a gut‐brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation‐predominant IBS (IBS‐C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta‐analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS‐C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow‐up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS‐C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis. 相似文献
6.
Tomoaki Matsuo Yoshio Nakata Yasutomi Katayama Motoyuki Iemitsu Seiji Maeda Tomohiro Okura Maeng‐Kyu Kim Hiroyuki Ohkubo Kikuko Hotta Kiyoji Tanaka 《Obesity (Silver Spring, Md.)》2009,17(10):1924-1931
Several studies indicate that expression of the peroxisome proliferator–activated receptor γ (PPARG) gene is influenced by calorie restriction. The aim of this study was to investigate whether PPARG gene variations are associated with weight reduction and changes in coronary heart disease (CHD) risk factors in response to a 14‐week calorie restriction. In total, 95 middle‐aged, Japanese women (BMI ≥25 kg/m2) enrolled as subjects for 14 weeks and attended weekly dietary lectures instructing them on how to consume a nutritionally balanced diet of 1,200 kcal/day. Eight single‐nucleotide polymorphisms (SNPs) in the PPARG gene (rs1801282 (Pro/Ala), rs2292101, rs2959272, rs1386835, rs709158, rs1175540, rs1175544, and rs1797912) were analyzed. Body weight decreased significantly (?7.7 ± 3.1 kg; ?11.3 ± 4.4%) during the intervention. Six PPARG SNPs (rs2959272, rs1386835, rs709158, rs1175540, rs1175544, and rs1797912) were significantly associated with the weight reduction, with rs1175544 having the strongest association (P = 0.004). No differences across the rs1175544 genotypes were observed in any of the blood analyses or in blood pressure. In a multiple regression analysis, the rs1175544 genotypes accounted for 7% of the total weight reduction variance. These data suggest that one SNP of the PPARG genotype accounted for a significant portion of the total body weight reduction variance in response to a short‐term intervention consisting of calorie restriction; however, no relationship was found between these SNPs and the changes in CHD risk factors which accompanied weight loss. 相似文献
7.
Deniz Kanca Uzay Gormus Bengu Tokat Allison P. Eronat Zehra Bugra Oğuz Ozturk Hulya Yilmaz-Aydogan 《Biochemical genetics》2017,55(2):168-182
Recently, subfraction analysis of serum low density lipoprotein (LDL) is considered to be a better predictor of the risk of coronary heart disease (CHD) compared to the other lipid parameters. The aim of this study was to examine the effects of the HDL-associated Taq1B (rs708272) SNP of cholesterol ester transfer protein (CETP) gene on serum LDL subfractions in patients with CHD. Serum lipid levels were measured enzymatically and LDL subfraction analysis was carried out by the Lipoprint System (Quantimetrix, CA, USA). The CETP rs708272 SNP was studied in 66 healthy controls and 79 patients with CHD receiving statin therapy by the PCR–RFLP technique. The CHD patients had elevated antiatherogenic LDL-1 subfraction (p = 0.042), decreased atherogenic IDL-C subfraction (p = 0.023), and total IDL (p = 0.030) levels compared to the healthy controls. The CETP rs708272 Taq1B minor B2 allele was associated with increased levels of antiatherogenic LDL-1 (B2: 0.40 ± 0.20 vs. B1B1: 0.25 ± 0.08, p = 0.004) and large-LDL (LDL 1–2) subfractions in the CHD group (B2 allele: 0.68 ± 0.41 vs. B1B1: 0.42 ± 0.20; p < 0.05), while it was associated with reduced levels of the large-LDL subfraction in healthy subjects (B2 allele: 0.29 ± 0.14 vs. B1B1: 0.54 ± 0.24; p = 0.017). However, there was no statistically significant association between the CETP rs708272 SNP and small dense LDL subfraction (LDL 3–7) and lipoprotein levels (p > 0.05). Our findings have indicated that the CETP rs708272 SNP together with statin therapy may show a favorable effect on antiatherogenic LDL-1 and large-LDL subfractions in CHD patients with an atherogenic effect on large-LDL subfraction in healthy subjects. Based on these results, it can be concluded that the effects of the CETP variation on LDL subfraction could change in cardiometabolic events such as CHD and statin therapy. 相似文献
8.
Wang Q Hunt SC Xu Q Chen YE Province MA Eckfeldt JH Pankow JS Song Q 《American journal of physiology. Heart and circulatory physiology》2006,291(6):H2752-H2757
Recent epidemiological studies have indicated that baseline C-reactive protein (CRP) levels may have value in prediction of cardiovascular risk. Using six tag single-nucleotide polymorphisms (SNPs) selected from our complete list of SNPs on the CRP gene, we investigated the association of CRP genotypes with plasma CRP levels and cardiovascular risk in the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study cohort (1,296 Caucasians, 48.5% male, 54.7 +/- 12.8 yr old). There was a significant trend toward association of CRP haplotypes with CRP levels (P = 0.045). SNP analysis indicated a highly significant association of SNP -757 (rs3093059, P = 0.0004) and SNP -286 (rs3091244, P = 0.0065) and a borderline association of SNP -7180 (rs1341665, P = 0.06) with CRP levels. Neither CRP haplotypes nor individual SNP genotypes were associated with intima-media thickness of the common carotid or internal carotid artery or the bifurcation of the carotid arteries. These results indicated a strong impact of local SNPs of the CRP gene on plasma CRP levels, but there was no direct evidence that these genetically controlled CRP elevations by local CRP SNPs contributed to cardiovascular disease phenotypes. 相似文献
9.
Li Ma Christie M. Ballantyne John W. Belmont Alon Keinan Ariel Brautbar 《Journal of lipid research》2012,53(11):2425-2428
The mixed dyslipidemia phenotype is characterized by elevated triglycerides (TG), low HDL cholesterol (HDL-C), increased ApoB levels, and premature coronary atherosclerosis. Fibrate-statin combination therapy reduces ApoB levels and coronary events in the mixed dyslipidemia population. We sought to identify gene-gene interactions that affect ApoB response to statin-fenofibric acid therapy in the mixed dyslipidemia population. Using a predefined subset of single-nucleotide polymorphisms (SNPs) that were previously associated with TG, VLDL, or HDL-C, we applied gene-gene interaction testing in a randomized, double-blind, clinical trial examining the response to fenofibric acid (FNA) and its combination with statin in 1,865 individuals with mixed dyslipidemia. Of 11,783 possible SNP pairs examined, we detected a single significant interaction between rs12130333, located within the ANGPTL3 gene region, and rs4240705, within the RXRA gene, on ApoB reduction after statin-FNA therapy (P = 4.0 × 10−6). ApoB response to therapy gradually reduced with the increasing number of T alleles in the rs12130333 but only in the presence of the GG genotype of rs4240705. Individuals doubly homozygous for the minor alleles at rs12130333 and rs4240705 showed a paradoxical increase of 1.8% in ApoB levels after FNA-statin combination therapy. No gene-gene interaction was identified other than an interaction between SNPs in the ANGPTL3 and RXRA regions, which results in the inhibition of ApoB reduction in response to statin-FNA therapy. Further study is required to examine the clinical applicability of this genetic interaction and its effect on coronary events. 相似文献
10.
Ahmed Al-Qahtani Mashael Al-Anazi Nisha A. Viswan Nisreen Khalaf Ayman A. Abdo Faisal M. Sanai Hamad Al-Ashgar Mohammed Al-Ahdal 《PloS one》2012,7(9)
Background/Aim
Kinesin family member 1B (KIF1B) gene resides in the chromosomal region 1p36.22 and has been reported to have frequent deletions in a variety of human cancers. A recent genome wide association study (GWAS) study conducted on a Chinese population has reported the involvement of a KIF1B genetic variant in Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). This study aims to investigate the significance of KIF1B genetic variations in HBV-associated hepatitis in patients of Saudi Arabian ethnicity.Methods
TaqMan genotyping assay was used to investigate the association of three SNPs (rs17401966, rs12734551, and rs3748578) in 584 normal healthy controls and 660 HBV-infected patients. The patients were categorized into inactive carriers (Case I), active carriers (Case II), Cirrhosis (Case III) and Cirrhosis-HCC (Case IV) sub-groups.Results
Since SNPs rs12734551 and rs3748578 are in strong linkage disequilibrium (LD) with rs17401966, only results for the latter SNP are reported. Therefore, the allele frequency of rs17401966 among HBV-infected patients and healthy controls were comparable and therefore, no significant association was observed (P = 0.2811, Odds Ratio (OR) 0.897). A similar analysis was performed among the different sub-groups in order to determine whether KIF1B SNPs were associated with the advancement of the disease. No significant differences were observed in any of the comparisons performed.Conclusion
Polymorphisms at KIF1B gene locus investigated in this study showed no significant association with HBV infection or with HBV-associated diseases such as liver cirrhosis or HCC. 相似文献11.
Lindstrom S Schumacher F Siddiq A Travis RC Campa D Berndt SI Diver WR Severi G Allen N Andriole G Bueno-de-Mesquita B Chanock SJ Crawford D Gaziano JM Giles GG Giovannucci E Guo C Haiman CA Hayes RB Halkjaer J Hunter DJ Johansson M Kaaks R Kolonel LN Navarro C Riboli E Sacerdote C Stampfer M Stram DO Thun MJ Trichopoulos D Virtamo J Weinstein SJ Yeager M Henderson B Ma J Le Marchand L Albanes D Kraft P 《PloS one》2011,6(2):e17142
Genome-wide association studies (GWAS) have identified multiple single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. However, whether these associations can be consistently replicated, vary with disease aggressiveness (tumor stage and grade) and/or interact with non-genetic potential risk factors or other SNPs is unknown. We therefore genotyped 39 SNPs from regions identified by several prostate cancer GWAS in 10,501 prostate cancer cases and 10,831 controls from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). We replicated 36 out of 39 SNPs (P-values ranging from 0.01 to 10−28). Two SNPs located near KLK3 associated with PSA levels showed differential association with Gleason grade (rs2735839, P = 0.0001 and rs266849, P = 0.0004; case-only test), where the alleles associated with decreasing PSA levels were inversely associated with low-grade (as defined by Gleason grade <8) tumors but positively associated with high-grade tumors. No other SNP showed differential associations according to disease stage or grade. We observed no effect modification by SNP for association with age at diagnosis, family history of prostate cancer, diabetes, BMI, height, smoking or alcohol intake. Moreover, we found no evidence of pair-wise SNP-SNP interactions. While these SNPs represent new independent risk factors for prostate cancer, we saw little evidence for effect modification by other SNPs or by the environmental factors examined. 相似文献
12.
Given the essential role of prolactin (PRL) and its receptor (PRLR) in breast tumorigenesis, we investigated whether single nucleotide polymorphisms (SNPs) in the PRL and PRLR genes were associated with breast cancer in Taiwanese women. A total of 160 breast cancer patients and 336 unrelated control Taiwanese women were enrolled in this study. Three SNPs (rs1341238, rs2244502 and rs3756824) in the PRL gene and one SNP (rs10941235) in the PRLR gene were genotyped using allele-specific polymerase chain reaction and DNA sequencing. We showed that the PRLR SNP rs10941235 was associated with breast cancer (P < 0.05) and its genotype frequencies in the breast cancer group were significantly associated (P < 0.05) with the levels of cancer antigen 15-3, a serum biomarker of breast cancer. The PRL SNP rs3756824 was significantly associated with breast cancer metastasis (P < 0.05). These findings suggest that the polymorphism rs10941235 in the PRLR gene is associated with breast cancer and cancer antigen 15-3 levels in Taiwanese women. 相似文献
13.
Lance A. Bare Edward A. Ruiz-Narvaéz Carmen H. Tong Andre R. Arellano Charles M. Rowland Joseph J. Catanese Frank M. Sacks James J. Devlin Hannia Campos 《PloS one》2010,5(9)
Background and Methodology
The 719Arg allele of KIF6 (rs20455) was associated with coronary events in Caucasian participants of five prospective studies. We investigated whether this KIF6 variant was associated with non-fatal myocardial infarction (MI) in a case-control study of an admixed population from the Central Valley of Costa Rica. Genotypes of the KIF6 variant were determined for 4,134 men and women. Cases (1,987) had survived a first MI; controls (2,147) had no history of MI and were matched to cases by age, sex, and area of residence. We tested the association between the KIF6 719Arg allele and non-fatal MI by conditional logistic regression and adjusted for admixture of founder populations.Principal Findings
Compared with the reference Trp/Trp homozygotes, KIF6 719Arg carriers were not at significantly higher risk for non-fatal MI in this study after adjustment for traditional risk factors or admixture (OR = 1.12; 95%CI, 0.98–1.28). Heterozygotes of the KIF6 Trp719Arg variant were at increased risk of non-fatal MI: the adjusted odds ratio was 1.16 (95% confidence interval, 1.01–1.34), but this association would not be significant after a multiple testing correction.Conclusions/Significance
We found that carriers of the KIF6 719Arg allele were not at increased risk of non-fatal MI in a case-control study of Costa Ricans living in the Central Valley of Costa Rica. 相似文献14.
N. R. Hoft R. P. Corley M. B. McQueen D. Huizinga S. Menard M. A. Ehringer 《Genes, Brain & Behavior》2009,8(6):631-637
The CHRNA6 and CHRNB3 genes have been associated with nicotine dependence and early subjective response to nicotine. Here we present evidence, using a nationally representative sample of adults, that this region is also associated with alcohol behaviors. Six SNPs (single nucleotide polymorphisms) spanning the CHRNB3/A6 genes were analyzed using the statistical genetics software FBAT-PC, which allows one to examine a collection of multiple phenotypes to generate a maximally heritable composite phenotype for each SNP. The six SNPs were tested using FBAT-PC including four alcohol phenotypes: average number of drinks, blackouts, total number of DSM-IV abuse and dependence symptoms endorsed, and quit attempts. Three SNPs in CHRNA6 (rs1072003, P = 0.015; rs892413, P = 0.0033 and rs2304297, P = 0.012) and one SNP in CHRNB3 (rs13280604, P = 0.0053) were associated with a composite of the alcohol phenotypes. The association was primarily driven by the average number of drinks. 相似文献
15.
Hunt SC Hasstedt SJ Xin Y Dalley BK Milash BA Yakobson E Gress RE Davidson LE Adams TD 《Obesity (Silver Spring, Md.)》2011,19(11):2241-2247
Neuropeptide Y (NPY) is an appetite hormone that acts centrally to control feeding behavior. The 5' and exon 2 regions of NPY2R, one of five NPY receptor genes, have been weakly and inconsistently implicated with obesity. With the ATG start site of the gene at the beginning of exon 2, single-nucleotide polymorphisms (SNPs) across intron 1 may show stronger associations with obesity than expected. Two 5' SNPs, three intron 1 SNPs, and one synonymous exon 2 SNP were genotyped on 2,985 white Utah subjects. Previously associated FTO, NPY, NPY1R, MC4R, PPARGC1A, OR7D4, and four NPFFR2 SNPs were also genotyped and related to BMI. One NPY2R 5' SNP (rs12649641, P = 0.008), an exon 2 SNP (rs2880415, P = 0.009), and an intron 1 SNP (rs17376826, P = 7 × 10(-6)) were each significantly associated with BMI. All three SNPs, plus FTO (rs9939609, P = 1.5 × 10(-6)) and two NPFFR2 SNPs (rs4129733, P = 3.7 × 10(-13) and rs11940196, 4.2 × 10(-10)) remained significant in a multiple regression additive model. Diplotypes using the estimated haplotypes of NPY2R, NPFFR2, and MC4R were significantly associated with BMI (P = 1.0 × 10(-10), 3.2 × 10(-8), and 1.1 × 10(-4), respectively). Haplotypes of NPY2R, NPFFR2, and MC4R, plus the FTO SNP, explained 9.6% of the BMI variance. SNP effect sizes per allele for the four genes ranged from 0.8 to 3.5 kg/m(2). We conclude that haplotypes containing the rs17376826 SNP in intron 1 of NPY2R have strong associations with BMI, some NPFFR2 haplotypes are strongly protective against or increase risk of obesity, and both NPY2R and NPFFR2 play important roles in obesity predisposition independent of FTO and MC4R. 相似文献
16.
《PloS one》2016,11(3)
Background
Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting.Methods
We performed a two-stage GWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898 MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5×10−6 in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with total mortality in individuals who experienced MI during follow-up.Results
In Stage I 15 loci passed the threshold of 5×10−6; 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value<8.8×10−3) and three exceeded the genome-wide significance threshold when Stage I and Stage II results were combined (top SNP rs6941513: p = 6.2×10−9). Despite excellent power, the 9p21 locus SNP (rs1333049) was only modestly associated with MI (HR = 1.09, p-value = 0.02) and marginally with CHD (HR = 1.06, p-value = 0.08). Among an inception cohort of those who experienced MI during follow-up, the risk allele of rs1333049 was associated with a decreased risk of subsequent mortality (HR = 0.90, p-value = 3.2×10−3).Conclusions
QKI represents a novel locus that may serve as a predictor of incident CHD in prospective studies. The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders. 相似文献17.
Zhong Chen Qi Qian Chengchun Tang Jiandong Ding Yi Feng Genshan Ma 《Molecular biology reports》2013,40(2):1021-1026
Two novel single nucleotide polymorphisms (SNPs; rs7529229 and rs2228145) in the interleukin-6 receptor (IL6R) gene have recently been associated with coronary heart disease (CHD) in a European population. We sought to replicate this finding and to investigate associations of these two SNPs with the severity and clinical phenotypes of premature CHD in a Chinese Han population. A total of 418 patients were studied, including 187 cases with coronary stenosis ≥50 % or acute myocardial infarction (males < 55 years and females < 65 years) and 231 controls without documented CHD. A ligase detection reaction was performed to detect rs7529229 and rs2228145. There were no differences between the controls and premature CHD groups in the frequencies for the three genotypes and alleles of rs7529229 and rs2228145 (all P > 0.05), nor did they differ between the two groups when grouped by gender (all P > 0.05). There were also no associations between these two SNPs and the severity of coronary lesions or clinical phenotypes of premature CHD (all P > 0.05). Our results do not support an association between rs7529229 or rs2228145 with premature CHD in the Chinese Han population. Further studies are warranted to elucidate the role of these two SNPs in the development of atherosclerosis and CHD. 相似文献
18.
Mona Dverdal Jansen Gun Peggy Knudsen Ronny Myhre Gudrun Høiseth Jørg Mørland Øyvind Næss Kristian Tambs Per Magnus 《Molecular biology reports》2014,41(5):2733-2743
Single nucleotide polymorphisms (SNPs) in loci 1p13 and 9p21 have previously been found to be associated with incident coronary heart disease (CHD). This study aimed to investigate whether these SNPs show associations with fatal CHD in a population-based cohort study after adjustment for socioeconomic- and lifestyle-related CHD risk factors not commonly included in genetic association studies. Using the population-based Cohort of Norway (CONOR), a nested case-cohort study was set up and DNA from 2,953 subjects (829 cases and 2,124 non-cases) were genotyped. The association with fatal CHD was estimated for four SNPs, three from locus 1p13 and one from locus 9p21. Multivariable Cox regression was used to estimate unstratified and gender-stratified hazard ratios while adjusting for major CHD risk factors. The associations between three SNPs from locus 1p13 and non-HDL cholesterol levels were also estimated. Men homozygous for the risk alleles on rs1333049 (9p21) and rs14000 (1p13) were found to have significantly increased hazard ratios in crude and adjusted models, and the hazard ratios remained statistically significant when both genders were analyzed together. Adjustment for additional socioeconomic- and lifestyle-related CHD risk factors influenced the association estimates only slightly. No significant associations were observed between the other two SNPs in loci 1p13 (rs599839 and rs646776) and CHD mortality in either gender. Both rs599839 and rs646776 showed significant, gradual increases in non-HDL cholesterol levels with increasing number of risk alleles. This study confirms the association between 9p21 (rs1333049) and fatal CHD in a Norwegian population-based cohort. The effect was not influenced by several socioeconomic- and lifestyle-related risk factors. Our results show that 1p13 (rs14000) may also be associated with fatal CHD. SNPs at 1p13 (rs599839 and rs646776) were associated with non-HDL cholesterol levels. 相似文献
19.
Xu Han Lixuan Gui Bing Liu Jing Wang Yaru Li Xiayun Dai Jun Li Binyao Yang Gaokun Qiu Jing Feng Xiaomin Zhang Tangchun Wu Meian He 《BMC genetics》2015,16(1)
Background
Multiple studies investigated the associations between serum uric acid and coronary heart disease (CHD) risk. However, further investigations still remain to be carried out to determine whether there exists a causal relationship between them. We aim to explore the associations between genetic variants in uric acid related loci of SLC2A9 and ABCG2 and CHD risk in a Chinese population.Results
A case–control study including 1,146 CHD cases and 1,146 controls was conducted. Association analysis between two uric acid related variants (SNP rs11722228 in SLC2A9 and rs4148152 in ABCG2) and CHD risk was performed by logistic regression model. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Compared with subjects with A allele of rs4148152, those with G allele had a decreased CHD risk and the association remained significant in a multivariate model. However, it altered to null when BMI was added into the model. No significant association was observed between rs11722228 and CHD risk. The distribution of CHD risk factors was not significantly different among different genotypes of both SNPs. Among subjects who did not consume alcohol, the G allele of rs4148152 showed a moderate protective effect. However, no significant interactions were observed between SNP by CHD risk factors on CHD risk.Conclusions
There might be no association between the two uric acid related SNPs with CHD risk. Further studies were warranted to validate these results.Electronic supplementary material
The online version of this article (doi:10.1186/s12863-015-0162-7) contains supplementary material, which is available to authorized users. 相似文献20.
Wan Khairunnisa Wan Juhari Nur Aida Md Tamrin Mohd Hanif Ridzuan Mat Daud Hatin Wan Isa Nurfazreen Mohd Nasir Sathiya Maran Nur Shafawati Abdul Rajab Khairul Bariah Ahmad Amin Noordin Nik Norliza Nik Hassan Rick Tearle Rozaimi Razali Amir Feisal Merican Bin Alwi Zilfalil 《The HUGO journal》2014,8(1)
BackgroundThe sequencing of two members of the Royal Kelantan Malay family genomes will provide insights on the Kelantan Malay whole genome sequences. The two Kelantan Malay genomes were analyzed for the SNP markers associated with thalassemia and Helicobacter pylori infection. Helicobacter pylori infection was reported to be low prevalence in the north-east as compared to the west coast of the Peninsular Malaysia and beta-thalassemia was known to be one of the most common inherited and genetic disorder in Malaysia.ResultBy combining SNP information from literatures, GWAS study and NCBI ClinVar, 18 unique SNPs were selected for further analysis. From these 18 SNPs, 10 SNPs came from previous study of Helicobacter pylori infection among Malay patients, 6 SNPs were from NCBI ClinVar and 2 SNPs from GWAS studies. The analysis reveals that both Royal Kelantan Malay genomes shared all the 10 SNPs identified by Maran (Single Nucleotide Polymorphims (SNPs) genotypic profiling of Malay patients with and without Helicobacter pylori infection in Kelantan, 2011) and one SNP from GWAS study. In addition, the analysis also reveals that both Royal Kelantan Malay genomes shared 3 SNP markers; HBG1 (rs1061234), HBB (rs1609812) and BCL11A (rs766432) where all three markers were associated with beta-thalassemia.ConclusionsOur findings suggest that the Royal Kelantan Malays carry the SNPs which are associated with protection to Helicobacter pylori infection. In addition they also carry SNPs which are associated with beta-thalassemia. These findings are in line with the findings by other researchers who conducted studies on thalassemia and Helicobacter pylori infection in the non-royal Malay population. 相似文献